The appearance of a beta-migrating lipoprotein in the d less than 1.006 g/ml fraction (beta-VLDL) has been reported in numerous experimental animals in response to the feeding of various atherogenic diets. These lipoproteins are similar to beta-VLDL described in human patients with Type III hyperlipoproteinemia and are triglyceride-poor and cholesteryl-ester enriched when compared to normally occurring VLDL. We propose to study the effects of casein vs. soya protein, sucrose vs. dextrose, and high saturated vs. high unsaturated fat containing semi-synthetic diets on the production of beta-VLDL in the rabbit. A unified and systematic approach correlating the types of dietary protein, carbohydrate and fat with the appearance of beta-VLDL, aortic lesions and hepatic cholesterogenesis is planned. Further, the characterization of the properties of both beta-VLDL and IDL (1.006 g/ml less than d less than 1.019 g/ml) via agarose and sodium-dodecyl sulface polyacrylamide gel electrophoresis and transmission electron microscopy will be accomplished. Evidence for the possible involvement of 14C-cholesterol labeled beta-VLDL in atherogenesis via the incorporation of this label into the atherosclerotic lesion will also be obtained. The role of the lipoprotein lipase system on beta-VLDL and IDL lipolysis in vivo using fluorescent probes will be studied in order to help explain the build-up of these lipoproteins in rabbits fed the various experimental diets. This data will subsequently be compared with the in vitro lipolysis of these lipoproteins using both radiolabeled natural and artificial substrates due to post-heparin plasma triglyceride hydrolase preparations. Lastly, the substrate specificity of purified rabbit heart lipoprotein lipase for fatty acyl chains using both natural and artificial substrate will be studied. These experiments are designed to evaluate the potential atherogenic nature of the latered and intermediate lipoprotein fractions observed in response to the feeding of semi-synthetic atherogenic diets in the rabbit model.